Association of Prophylactic Intravenous Corticosteroid Premedication With Toxicity and Survival in Patients Receiving Enfortumab Vedotin for Locally Advanced or Metastatic Urothelial Carcinoma

OBJECTIVES: Enfortumab vedotin (EV) is the standard treatment for locally advanced or metastatic urothelial carcinoma (la/mUC), though skin toxicities are problematic. We evaluated whether prophylactic corticosteroid premedication is associated with reduced toxicity and survival outcomes. METHODS: We retrospectively analyzed 157 patients with la/mUC receiving EV monotherapy, stratified by prophylactic intravenous dexamethasone (6.6 mg) premedication (pre-EV steroid, n = 20) or not (no pre-EV steroid, n = 137). Endpoints included the incidence of EV-related adverse events (AEs), objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Inverse probability of treatment weighting (IPTW) was used to adjust for baseline imbalances. RESULTS: Corticosteroid premedication was associated with a significantly lower incidence of skin AEs (10% vs. 62.7%, p < 0.001) and a reduced number of cumulative AEs (median 1 vs. 2, p = 0.018). The ORR were comparable. However, patients with steroid premedication showed inferior OS compared to those without (median OS 10.3 vs. 17.4 months, p = 0.008), while PFS showed no significant difference. Multivariable analysis confirmed corticosteroid premedication as an independent predictor of reduced skin AEs (OR 0.08, p = 0.001); however, it was associated with worse OS (HR 1.91, p = 0.048), with no significant impact on PFS. In the IPTW-adjusted analysis, corticosteroid premedication remained significantly associated with worse OS. CONCLUSIONS: Corticosteroid premedication reduces skin toxicities during EV monotherapy, but its impact on survival remains uncertain and requires validation in larger studies.